MicroRNA-125b Induces Metastasis by Targeting STARD13 in MCF-7 and MDA-MB-231 Breast Cancer Cells

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by targeting mRNAs to trigger either translation repression or mRNA degradation. miR-125b is down-regulated in human breast cancer cells compared with the normal ones except highly metastatic tumor cells MDA-MB-231. However, few functional studies were designed to investigate metastatic potential of miR-125b. In this study, the effects of miR-125b on metastasis in human breast cancer cells were studied, and the targets of miR-125b were also explored. Transwell migration assay, cell wound healing assay, adhesion assay and nude mice model of metastasis were utilized to investigate the effects of miR-125b on metastasis potential in vitro and in vivo. In addition, it was implied STARD13 (DLC2) was a direct target of miR-125b by Target-Scan analysis, luciferase reporter assay and western blot. Furthermore, activation of STARD13 was identified responsible for metastasis induced by miR-125b through a siRNA targeting STARD13. qRT-PCR, immunofluorescent assay and western blot was used to observe the variation of Vimentin and α-SMA in breast cancer cells. In summary, our study provided new insights into the function of miR-125b during the metastasis of breat cancer cells and also suggested the role of miR-125b in pro-metastasis by targeting STARD13.

Elevated microRNA-125b levels predict a worse prognosis in HER2-positive breast cancer patients

“…In the present study, it was found that miR-125b expression was significantly increased in breast cancer tissues compared to those of noncancerous tissues, and high miR-125b expression indicated a poor prognosis in breast cancer patients. Tang et al demonstrated that upregulation of miR-125b was able to activate the metastatic activities of breast cancer cells in vivo and in vitro by inducing breast cancer cells to obtain epithelial and mesenchymal characteristics while regulating the reorganization of actin cytoskeleton through the STARD13-Ras homologue gene family member A-Rho-associated protein kinase signaling pathway (13). Consistently, the present results showed that miR-125b expression was correlated with clinical TNM stages.…”

“…In addition, miR-125b-overexpressing breast cancer cells were impaired in their anchorage-dependent growth and exhibited reduced migration and invasion capacities (12). However, miR-125b can also induce metastasis by targeting StAR related lipid transfer domain containing 13 (STARD13) in MCF-7 and MDA-MB-231 breast cancer cells (13). Our previous study demonstrated that upregulation of miR-125b conferred a chemoresistant phenotype by targeting B-cell lymphoma 2 antagonist killer 1 (Bak1) (14), and other previous data showed that miR-125b could maintain cancer stem-like side population fraction (15).…”

Detection and quantification of extracellular microRNAs in medulloblastoma

“…[40][41][42][43][44] Our observations provide indirect evidence supporting the hypothesis that ex-miRNA are possible facilitators of metastasis by modifying local or distal microenvironments. [45] However, further studies are needed using counter-regulation of key ex-miRNA expression to determine their effect on regulation of motility, migration, and invasion of MB cells.…”

The regulation of rhoA by stard 13 in focal adhesions is essential for astrocytoma cell motility. (c2013)

“…StarD13 was also found to inhibit cell motility in hepatocellular carcinoma, which was consistent with its role as a tumor suppressor (Tang et al, 2012). However, its role in astrocytoma has never been studied.…”

“…This further confirms that the loss of StarD13 in cells transfected with the StarD13 siRNA is indeed responsible for the decrease in cell motility observed. Previous reports that investigated the role of StarD13 in cell motility showed that it negatively regulates motility (Tang et al, 2012). However, there are no previous reports on the role of StarD13 in astrocytoma or glioblastoma cells.…”